ReviewThe Biochemical journal2021
PHLPPing the balance: restoration of protein kinase C in cancer.
Review in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Sex-specific disruptions in PKCγ signaling in a mouse model of spinocerebellar ataxia type 14.JCI insight · 2026Article
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Functional specificity in biomolecular condensates revealed by genetic complementation.Nature reviews. Genetics · 2025Review
- Cancer-associated mutations in protein kinase C theta are loss-of-function.The Biochemical journal · 2024Article
- A common molecular and cellular pathway in developing Alzheimer and cancer.Biochemistry and biophysics reports · 2024Review
- Article
- Single-residue mutation in protein kinase C toggles between cancer and neurodegeneration.The Biochemical journal · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- PDK1:PKCα heterodimer association-dissociation dynamics in single-molecule diffusion tracks on a target membrane.Biophysical journal · 2023Article
- A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.The Journal of clinical investigation · 2023Article
- Emerging roles of PHLPP phosphatases in lung cancer.Frontiers in oncology · 2023Review
- Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model.Nature communications · 2022Article
- Mutations in protein kinase Cγ promote spinocerebellar ataxia type 14 by impairing kinase autoinhibition.Science signaling · 2022Article
- Protein kinase C: release from quarantine by mTORC2.Trends in biochemical sciences · 2022Review
- mTOR Regulation of AGC Kinases: New Twist to an Old Tail.Molecular pharmacology · 2022Review
- Two Sides of the Same Coin: Protein Kinase C γ in Cancer and Neurodegeneration.Frontiers in cell and developmental biology · 2022Review
- Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?Neuronal signaling · 2021Review
- Emerging roles of PHLPP phosphatases in metabolism.BMB reports · 2021Review
- Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Protein kinase signalling, which transduces external messages to mediate cellular growth and metabolism, is frequently deregulated in human disease, and specifically in cancer. As such, there are 77 kinase inhibitors currently approved for the treatment of human disease by the FDA. Due to their historical association as the receptors for the tumour-promoting phorbol esters, PKC isozymes were initially targeted as oncogenes in cancer. However, a meta-analysis of clinical trials with PKC inhibitors in combination with chemotherapy revealed that these treatments were not advantageous, and instead resulted in poorer outcomes and greater adverse effects. More recent studies suggest that instead of inhibiting PKC, therapies should aim to restore PKC function in cancer: cancer-associated PKC mutations are generally loss-of-function and high PKC protein is protective in many cancers, including most notably KRAS-driven cancers. These recent findings have reframed PKC as having a tumour suppressive function. This review focusses on a potential new mechanism of restoring PKC function in cancer - through targeting of its negative regulator, the Ser/Thr protein phosphatase PHLPP. This phosphatase regulates PKC steady-state levels by regulating the phosphorylation of a key site, the hydrophobic motif, whose phosphorylation is necessary for the stability of the enzyme. We also consider whether the phosphorylation of the potent oncogene KRAS provides a mechanism by which high PKC expression may be protective in KRAS-driven human cancers.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.